Metformin to Treat Corticosteroids-induced Hyperglycemia

The Effect of Metformin in Pregnant Women Who Received Antenatal Corticosteroids on Glycemic Control and the Rate of Neonatal Hypoglycemia - Multicenter Prospective Randomized, Controlled Trial

Antenatal corticosteroids, particularly, betamethasone is routinely administered to pregnant women at risk for preterm delivery to improve neonatal outcomes.

Although antenatal betamethasone was shown to induce both maternal hyperglycemia and neonatal hypoglycemia, to date, there is insufficient data to establish whether treatment for maternal hyperglycemia, particularly, metformin, will decrease the risk for neonatal hypoglycemia, particularly of preterm neonates.

In the present study the investigators will examine the effect of treatment with metformin on maternal glycemic control and hypoglycemia in preterm neonates following maternal betamethasone treatment.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Preterm; Glycemic Control; Corticosteroids Induced Hyperglycemia
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 323
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Enav Yefet, MD/PhD; Phone Number: 972-46652306; Email: enyefet@poria.health.gov.il

Study Locations

• Israel
  • Afula, Israel
    • Recruiting
    • Emek Medical Center
    • Contact: Zohar Nachum
    • Principal Investigator: Zohar Nachum
  • Nahariya, Israel
    • Recruiting
    • Galilee Medical Center
    • Principal Investigator: Maya Wolf
  • Safed, Israel
    • Not yet recruiting
    • Ziv Medical Center
    • Contact: David Peleg
    • Principal Investigator: David Peleg
  • North
    • Tiberias, North, Israel, 15208
      • Recruiting
      • Baruch Padeh Medical center, Poriya
      • Contact: Enav Yefet, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women receiving betamethasone from 24 to 36.5 gestational weeks
• Before or within 24 hours following the first dose of betamethasone
• ≥18 years old

Exclusion Criteria:

• Women with pre-gestational and gestational diabetes mellitus (GDM)
• Known allergic sensitivity to metformin
• Known chronic heart failure
• Known chronic renal failure
• Refuse to participate
• Refuse to perform glucose challenge test/glucose tolerance test later on

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin group	Drug: Metformin; Metformin tablets according to glycemic control. Initial dose: 425 mg before meals (breakfast, lunch and supper) and 1700 mg around 22:00. Modifications may take place according to glycemic control
No Intervention: No treatment group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean maternal daily glucose values	According to daily glucose charts	Up to 4 days
The rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks)		Up to 7 days after delivery or discharge (which ever comes first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean maternal daily pre-prandial glucose values	According to daily glucose charts	Up to 4 days
Mean maternal daily post-prandial glucose values	According to daily glucose charts	Up to 4 days
Percent of abnormal values in the daily glucose chart	According to daily glucose charts	Up to 4 days
Rate of cesarean sections and operative deliveries		At delivery
Rate of neonates who will be admitted to the neonatal intensive care unit	APGAR scale of 0-worst and 10-best	Up to a week after delivery
Apgar score at 1 and 5 minutes		At delivery
Cord blood pH levels (when taken)		At delivery
The rate of neonates with hyperbilirubinemia		Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean head circumference		Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean birth weight		at delivery
The rate of fetal malformations and developmental disorders		Up to 7 days after delivery or discharge (which ever comes first)
Mean and lowest neonatal blood glucose values in preterm neonates		Up to 7 days after delivery or discharge (which ever comes first)
The rate of maternal adverse effects		48 hours

Collaborators and Investigators

• Sponsor: The Baruch Padeh Medical Center, Poriya

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 29, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 21-20POR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared according to the local review board regulations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No